Description

Product Description

SHLP-4 (Small Humanin-Like Peptide 4) is a mitochondrial-derived peptide (MDP) encoded by the 16S ribosomal RNA gene (MT-RNR2). It belongs to a class of microproteins produced from mitochondrial transcripts that function as signaling peptides regulating metabolism, apoptosis, and mitochondrial bioenergetics.

Discovered as part of the Humanin-like peptide family (SHLP1–6), SHLP-4 has been identified as a bioactive peptide that promotes cell proliferation, enhances mitochondrial activity, and contributes to systemic energy regulation. Unlike traditional nuclear-encoded proteins, SHLP-4 is translated from mitochondrial RNA, emphasizing the dynamic role of mitochondrial genomes in controlling cellular physiology.

Biological Context

Mitochondria are central regulators of cellular homeostasis and play crucial roles in energy metabolism, apoptosis, and reactive oxygen species (ROS) production. The discovery of mitochondrial-derived peptides (MDPs) such as Humanin, MOTS-c, and SHLPs revealed that mitochondria actively communicate with the nucleus and cytoplasm through peptide signaling.

SHLP-4, specifically, has demonstrated cell-protective and proliferative properties in pancreatic β-cell and cardiovascular models. In murine insulinoma NIT-1 cells, SHLP-4 increases cell viability and proliferation, suggesting a role in pancreatic cell regeneration. Its expression and activity patterns also link it to cardiovascular protection, where mitochondrial peptides modulate oxidative stress, cell survival, and energy metabolism in cardiac tissues.

Research Applications

SHLP-4 is a key molecule for exploring the interface between mitochondrial signaling and metabolic diseases:

• Diabetes Research: Supports pancreatic β-cell proliferation and insulin secretion under stress conditions.

• Cardiovascular Studies: Investigates mitochondrial signaling in cardiac protection and endothelial function.

• Metabolic Regulation: Examines mitochondrial peptides’ role in energy expenditure and glucose metabolism.

• Aging and Cellular Homeostasis: Studies mitochondrial-nuclear crosstalk in maintaining cellular vitality.

Key Biological Features

• Increases mitochondrial oxygen consumption rate (OCR) and ATP production.

• Stimulates cell proliferation in insulinoma and cardiovascular models.

• Protects against oxidative stress-induced apoptosis.

• Regulates mitochondrial dynamics (fission and fusion balance).

• Modulates intracellular calcium levels, contributing to improved cellular resilience.

Through these mechanisms, SHLP-4 represents a new class of endogenous mitochondrial signals that maintain energy balance, metabolic flexibility, and tissue integrity.

Product Specifications

Mechanism of Action

1. Regulation of Mitochondrial Function

SHLP-4 enhances mitochondrial respiration efficiency, increasing oxygen consumption rate (OCR) and ATP generation. By activating mitochondrial complexes I and IV, it improves oxidative phosphorylation, thereby sustaining cellular energy demands under stress.

2. Cytoprotection and Cell Proliferation

In pancreatic β-cells (NIT-1) and cardiovascular tissues, SHLP-4 promotes proliferation by activating PI3K/AKT and AMPK signaling pathways. These pathways are key regulators of energy sensing and cell growth. The peptide also helps preserve mitochondrial integrity, stabilizing the mitochondrial membrane potential (ΔΨm).

3. Oxidative Stress Reduction

SHLP-4 mitigates oxidative stress by upregulating antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx). It limits ROS accumulation, preventing oxidative damage to mitochondrial DNA and cellular membranes.

4. Mitochondrial-Nuclear Crosstalk

By acting as a signaling molecule, SHLP-4 bridges mitochondrial metabolic status and nuclear gene expression. It may upregulate genes involved in metabolic adaptation, antioxidant response, and cellular longevity, contributing to overall metabolic resilience.

5. Cardiovascular Protection

In cardiac models, SHLP-4 improves mitochondrial efficiency, reduces ischemia-induced ROS, and preserves cardiomyocyte viability. These effects point to its potential role as a mitochondrial cardioprotective peptide, balancing energy and redox homeostasis during oxidative or metabolic stress.

Collectively, SHLP-4 functions as a metabolic enhancer and cytoprotective factor, orchestrating a balance between energy production, redox regulation, and cellular proliferation.

Side Effects

SHLP-4 is a research peptide, and no toxicological data for clinical use exist. However, experimental and theoretical observations suggest possible effects:

• Excessive Mitochondrial Activation: May lead to overproduction of ATP or mild ROS imbalance in high concentrations.

• Altered Cell Cycle Regulation: Continuous proliferation signals could affect non-target tissues in vitro.

• Insulin Signaling Modulation: Could influence glucose uptake beyond intended levels.

• Metabolic Overcompensation: Long-term exposure may alter cellular energy equilibrium.

• Immune Response Sensitivity: Possible modulation of inflammatory cytokine levels in tissue studies.

Researchers are advised to use appropriate dosage control and to interpret results within physiological relevance.

Disclaimer

For research use only. Not intended for human or veterinary use, diagnosis, or treatment.

Keywords

SHLP-4, CAS 1191923-94-0,Small Humanin-Like Peptide 4, mitochondrial-derived peptide, MT-RNR2, mitochondrial bioenergetics, cell proliferation, oxidative stress, ATP production, diabetes research, cardiovascular research, mitochondrial signaling.

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